Closed tip dynamic microvalve protection device

ABSTRACT

A method includes providing microvalve device having inner and outer catheters, and a filter valve attached to the distal end of the inner and outer catheters. Longitudinal displacement of the inner catheter relative to the outer catheter moves the filter valve from a non-deployed configuration to a deployed configuration. With the inner catheter longitudinally advanced a first amount relative to the outer catheter, the filter valve is in a reduced first diameter for advancement of a guidewire to a target location. Once the filter valve reaches the target location, the inner catheter is moved relative to the outer catheter such that the filter valve assumes a larger second diameter. A therapeutic agent is infused through the inner catheter and beyond the filter valve.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 14/330,456, filedJul. 14, 2014, to be issued as U.S. Pat. No. 9,968,740, which is acontinuation-in-part of U.S. Ser. No. 14/259,293, filed Apr. 23, 2014,now issued as U.S. Pat. No. 9,770,319, which claims benefit of U.S.Provisional No. 61/970,202, filed Mar. 25, 2014, all of which are herebyincorporated by reference herein in their entireties.

This application is related to U.S. Pat. Nos. 8,500,775 and 8,696,698,which are hereby incorporated by reference herein in their entireties.

BACKGROUND OF THE INVENTION 1. Field of Invention

The present invention relates generally to a valve for performing amedical embolizing treatment, and particularly to a valve that increasespenetration of a treatment agent into targeted blood vessels and reducesreflux of the treatment agent into non-targeted vessels.

2. State of the Art

Embolization, chemo-embolization, and radio-embolization therapy areoften clinically used to treat a range of diseases, such ashypervascular liver tumors, uterine fibroids, secondary cancermetastasis in the liver, pre-operative treatment of hypervascularmenangiomas in the brain and bronchial artery embolization forhemoptysis. An embolizing agent may be embodied in different forms, suchas beads, liquid, foam, or glue placed into an arterial vasculature. Thebeads may be uncoated or coated. Where the beads are coated, the coatingmay be a chemotherapy agent, a radiation agent or other therapeuticagent. When it is desirable to embolize a small blood vessel, small beadsizes (e.g., 10 μm-100 μm) are utilized. When a larger vessel is to beembolized, a larger bead size (e.g., 100 μm-900 μm) is typically chosen.

While embolizing agent therapies which are considered minimally orlimited invasive have often provided good results, they have a smallincidence of non-targeted embolization which can lead to adverse eventsand morbidity. Infusion with an infusion microcatheter allowsbi-directional flow. That is, the use of a microcatheter to infuse anembolic agent allows blood and the infused embolic agent to move forwardin addition to allowing blood and the embolic agent to be pushedbackward (reflux). Reflux of a therapeutic agent causes non-targetdamage to surrounding healthy organs. In interventional oncologyembolization procedures, the goal is to bombard a cancer tumor witheither radiation or chemotherapy. It is important to maintain forwardflow throughout the entire vascular tree in the target organ in order todeliver therapies into the distal vasculature, where the therapy can bemost effective. This issue is amplified in hypovascular tumors or inpatients who have undergone chemotherapy, where slow flow limits thedose of therapeutic agent delivered and reflux of agents to non-targettissue can happen well before the physician has delivered the desireddose.

The pressure in a vessel at multiple locations in the vascular treechanges during an embolic infusion procedure. Initially, the pressure ishigh proximally, and decreases over the length of the vessel. Forwardflow of therapy occurs when there is a pressure drop. If there is nopressure drop over a length of vessel, therapy does not flow downstream.If there is a higher pressure at one location, such as at the orifice ofa catheter, the embolic therapy flows in a direction toward lowerpressure. If the pressure generated at the orifice of an infusioncatheter is larger than the pressure in the vessel proximal to thecatheter orifice, some portion of the infused embolic therapy travels upstream (reflux) into non-target vessels and non-target organs. Thisphenomenon can happen even in vessels with strong forward flow if theinfusion pressure (pressure at the orifice of the catheter) issufficiently high.

During an embolization procedure, the embolic agents clog distal vesselsand block drainage of fluid into the capillary system. This leads to anincrease in the pressure in the distal vasculature. With the increasedpressure, there is a decrease in the pressure gradient and thereforeflow slows or stops in the distal vasculature. Later in the embolizationprocedure, larger vessels become embolized and the pressure increasesproximally until there is a system that effectively has constantpressure throughout the system. The effect is slow flow even in thelarger vessels, and distally the embolic agent no longer advances intothe target (tumor).

In current clinical practice with an infusion catheter, the physicianattempts to infuse embolics with pressure that does not cause reflux. Indoing this, the physician slows the infusion rate (and infusionpressure) or stops the infusion completely. The clinical impact ofcurrent infusion catheters and techniques is two fold: low doses of thetherapeutic embolic is delivered and there is poor distal penetrationinto the target vessels.

Additionally, reflux can be a time-sensitive phenomenon. Sometimes,reflux occurs as a response to an injection of the embolic agent, wherethe reflux occurs rapidly (e.g., in the time-scale of milliseconds) in amanner which is too fast for a human operator to respond. Also, refluxcan happen momentarily, followed by a temporary resumption of forwardflow in the blood vessel, only to be followed by additional reflux.

FIG. 1 shows a conventional (prior art) embolization treatment in thehepatic artery 106. Catheter 101 delivers embolization agents (beads)102 in a hepatic artery 106, with a goal of embolizing a target organ103. It is important that the forward flow (direction arrow 107) ofblood is maintained during an infusion of embolization agents 102because the forward flow is used to carry embolization agents 102 deepinto the vascular bed of target organ 103.

Embolization agents 102 are continuously injected until reflux ofcontrast agent is visualized in the distal area of the hepatic artery.Generally, since embolization agents 102 can rarely be visualizeddirectly, a contrast agent may be added to embolization agents 102. Theaddition of the contrast agent allows for a visualization of the refluxof the contrast agent (shown by arrow 108), which is indicative of thereflux of embolization agents 102. The reflux may, undesirably, causeembolization agents 102 to be delivered into a collateral artery 105,which is proximal to the tip of catheter 101. The presence ofembolization agents 102 in collateral artery 105 leads to non-targetembolization in a non-target organ 104, which may be the other lobe ofthe liver, the stomach, small intestine, pancreas, gall bladder, orother organ.

Non-targeted delivery of the embolic agent may have significant unwantedeffects on the human body. For example, in liver treatment, non-targeteddelivery of the embolic agent may have undesirable impacts on otherorgans including the stomach and small intestine. In uterine fibroidtreatment, the non-targeted delivery of the embolic agent may embolizeone or both ovaries leading to loss of menstrual cycle, subtle ovariandamage that may reduce fertility, early onset of menopause and in somecases substantial damage to the ovaries. Other unintended adverse eventsinclude unilateral deep buttock pain, buttock necrosis, and uterinenecrosis.

Often, interventional radiologists try to reduce the amount and impactof reflux by slowly releasing the embolizing agent and/or by deliveringa reduced dosage. The added time, complexity, increased x-ray dose tothe patient and physician (longer monitoring of the patient) andpotential for reduced efficacy make the slow delivery of embolizationagents suboptimal. Also, reducing the dosage often leads to the need formultiple follow-up treatments. Even when the physician tries to reducethe amount of reflux, the local flow conditions at the tip of thecatheter change too fast to be controlled by the physician, andtherefore rapid momentary reflux conditions can happen throughoutinfusion.

U.S. Pat. No. 8,696,698, previously incorporated herein, describes amicrovalve infusion system for infusing an embolic agent to a treatmentsite in a manner that overcomes many of the issues previously identifiedwith infusion using an infusion catheter alone. Referring to prior artFIGS. 2A and 2B, the microvalve infusion system 200 includes adynamically adjustably filter valve 202 coupled to the distal end of adelivery catheter 204. The delivery catheter and filter valve extendwithin an outer catheter 206. The filter valve 202 is naturally springbiased by its construction of filamentary elements 208 to automaticallypartially expand within a vessel when it is deployed from the outercatheter 206, and is coated with a polymer coating 210 that has a poresize suitable to filter an embolic therapeutic agent. More particularly,the filter valve 202 has an open distal end 212 and is coupled relativeto the delivery catheter 204 such that an embolic agent infused throughthe delivery catheter 204 and out of the distal orifice 214 of thedelivery catheter 204 exits within the interior 216 of the filter valve.In view of this construction, upon infusion, an increase in fluidpressure results within the filter valve and causes the filter valve 202to open, extend across a vessel, and thereby prevent reflux of theinfused embolic agent. In addition, as the fluid is pressurized throughthe delivery catheter and into the filter valve, the downstream pressurein the vessel is increased which facilitates maximum uptake into thetarget tissue for therapeutically delivered agents. Further, the filtervalve is responsive to local pressure about the valve which therebyenables substantially unrestricted forward flow of blood in the vessel,and reduces or stops reflux (regurgitation or backward flow) ofembolization agents which are introduced into the blood.

However, the devices in U.S. Pat. No. 8,696,698 have certain issues thatmay not always be advantageous. In various disclosed FIG. 44, thedevices shown have a large distal diameter which limits trackability intortuous branching vasculature. The distal end of the device in acollapsed, undeployed state is defined by the size of an outer catheter206, which can be significantly larger than the outer diameter deliverycatheter 204 that supports the filter valve 202 and significantly largerthan the outer diameter of a guidewire (not shown) used to the guide themicrovalve to the target location within the vessel. As such, trackingthe filter valve into the smaller vascular branches does not have adesired reliability. In addition, once the device is tracked to atreatment location, deployment of the filter valve requires that thefrictional force between the filter valve and the outer catheter beovercome. Overcoming such forces can potentially abrade the polymercoating on the filter valve. Improvements to such designs was providedin other figures disclosed in U.S. Pat. No. 8,696,698, so that the outerdiameter of the distal aspect of the device is reduced in size to in amanner that would faciliate tracking. However, once any of theembodiments of filter valve 202 in U.S. Pat. No. 8,696,698 are shown inthe open configuration, they assumes the shape of an open frustocone,which allows refluxing therapeutic embolic agent to enter the valve.This may lead to therapeutic agent remaining in the filter valve,particularly under conditions of slow forward flow within the vessel,which potentially could result in incomplete dosing.

SUMMARY OF THE INVENTION

An infusion device is provided that includes an outer catheter, andinner infusion catheter extending through the outer catheter, and adynamically adjustable filter valve coupled to both of the outer andinner catheters. The filter valve is formed from a naturallyspring-biased filamentary construction that is biased to radially expandand has a proximal end and a distal end. The proximal end of the filtervalve is coupled to a distal end of the outer catheter, and the distalend of the filter valve is coupled to a distal end of the innercatheter. The filter valve has a closed filtering distal portion, withthe proximal and distal portions of the valve separate by thecircumference about the maximum diameter of the filter valve. The innerinfusion catheter is configured to deliver a therapeutic embolic agentdistal of the closed distal portion of the filter valve.

The filter valve can be manually displaced between open and closedconfigurations by longitudinally displacing the distal end of the innercatheter relative to the distal end of the outer catheter. By displacingthe inner catheter distally relative to the outer catheter, the filtervalve is moved into a collapsed configuration, suitable for delivery tothe treatment site. In the collapsed configuration, the tip is taperedand assumes a form that has excellent trackability over a guidewire tobe advanced to a treatment site. To deploy the filter valve, the innercatheter is retracted relative to the outer catheter to cause the filtervalve to reconfigure, resulting in radial expansion toward a vesselwall. In addition, the spring-bias of the valve also operates to radialexpand the filter valve, particularly when subject to a pressuredifferential on opposing sides of the filter valve. In a preferredaspect of the invention, the proximal portion of the filter valve has adifferent radial expansion force than the distal portion of the filtervalve. More preferably, the proximal portion has a substantially greaterradial expansion force than the distal portion. Once the filter valve isin a deployed open configuration, i.e., with the distal tip in aretracted position relative to the delivery position, the filter valveis dynamically responsive to local pressure about the filter valve.Under the dynamically responsive operation, substantially unrestrictedforward flow of blood in the vessel is permitted, while backflow isprevented to stop reflux of the therapeutic agent within the vessel.

Upon retrieval of the infusion device at the end of the procedure theinner catheter can be further retracted into the outer catheter (suchthat the filter valve is substantially inverted and received within theouter catheter) to thereby capture and contain any therapeutic agentremaining on the filter valve.

BRIEF DESCRIPTION OF DRAWINGS

Prior art FIG. 1 shows a conventional embolizing catheter in a hepaticartery with embolizing agent refluxing into a non-targeted organ.

Prior art FIGS. 2A and 2B are schematic figures of a prior art filtervalve device shown in an undeployed configuration and a deployedconfiguration, respectively.

FIGS. 3A and 3B are schematic figures of an exemplary embodiment of atherapeutic filter valve device in a deployed state and an undeployedstate, respectively.

FIG. 4 is a schematic view of a shape of the distal end of a deployedfilter valve device.

FIG. 5 is a schematic view of another shape of the distal end of adeployed filter valve device.

FIG. 6A-6D are broken schematic diagrams of the exemplary embodiment ofthe filter valve device of FIGS. 3A and 3B, in use, with the distal endof the device illustrated positioned within a vessel.

FIG. 7 is perspective distal end photographic view of the distal end ofthe filter valve device in a deployed configuration.

FIGS. 8A-8C are schematic views of the distal end of the filter valvedevice in non-deployed and deployed configurations, indicating therespective positions of radio-opaque marker bands.

FIG. 9 is a graph indicating the variable pressure control distal of thefilter valve device.

FIGS. 10A-10C are schematic views of the deployed filter valve device,using variable pressure control to selectively infuse primary and branchvessels.

FIG. 11 is a schematic distal end view of an alternate coating constructfor the filter valve device.

FIG. 12 is a schematic distal end view of another coating construct forthe filter valve device.

FIG. 13 is a schematic distal end view of yet another alternate coatingconstruct for the filter valve device.

FIG. 14 is a schematic distal end view of a braid angle construct forany of the filter valve devices.

FIG. 15 is a schematic distal end view of another construct of for afilter valve device.

FIG. 16 is a schematic distal end view of yet another construct for afilter valve device.

FIGS. 17A-17C are schematic views of the distal end of still yet anotherconstruct for a filter valve device in non-deployed, partially deployed,and fully deployed configurations.

FIG. 18 is a distal end view of the filter valve device of FIGS.17A-17C, illustrating one arrangement for the wire filaments in thedistal portion of the filter valve.

FIG. 19 is a distal end view of a filter valve device, showing analternate arrangement for the wire filaments in the distal portion ofthe filter valve.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

With reference to the human body and components of the devices andsystems described herein which are intended to be hand-operated by auser, the terms “proximal” and “distal” are defined in reference to theuser's hand, with the term “proximal” being closer to the user's hand,and the term “distal” being further from the user's hand, unlessalternate definitions are specifically provided.

A first exemplary embodiment of a microvalve device 300 according to theinvention is seen in FIGS. 3A and 3B. It is noted that respectiveportions of the system illustrated in FIGS. 3A and 3B are not shownproportional to their intended size, but rather that the distal portionis illustrated significantly enlarged for purposes of explanation. Asshown in FIG. 3A, the device 300 includes a flexible outer catheter 302having a proximal end 304 and a distal end 306, a flexible innerdelivery catheter 308 extending through and longitudinally displaceablerelative to the outer catheter 304 and having a proximal end 310 and adistal end 312, and a filter valve 314 coupled to the distal ends 306,312 of the outer and inner catheters 304, 308. The proximal end 310 ofthe inner catheter is preferably mounted to a hub 316 with a rigidtubular coupling member 318. The tubular coupling member 318 ispreferably a stainless steel hypotube or similar structure. An infusionlumen 320 is defined from the hub 316 through to the distal end 312 ofthe inner catheter and is adapted for delivery of a therapeutic agent,including an embolizing agent, from outside the body of the patient (notshown) to a target vessel (artery or vein) in the patient. The proximalend 304 of the outer catheter 302 preferably includes a side arm port322 that is in fluid communication with an annular space 324 formedbetween the inner and outer catheters 304, 308 and extending into theinterior of the filter valve 314, and to flush the annular space 324 ofthe filter valve. Flushing such space, such as with a lubricant,including saline, operates to reduce friction between the inner andouter catheter to faciliate longitudinal movement therebetween.

A first radio-opaque marker band 326 is provided at the distal end 312of the inner catheter 308, and a second preferably larger radio-opaquemarker band 328 is provided at the distal end 306 of the outer catheter302. A third radio-opaque marker band 330 is provided to the innercatheter 308 in a defined positional relationship relative to the secondmarker band 328. By example, the third marker band 330 may beco-longitudinally positioned with the second marker band 328 when theinner and outer catheters 302, 308 are positioned to cause the filtervalve 314 to be in a deployed configuration, as shown in FIG. 3A anddiscussed below. FIG. 3B illustrates the microvalve device 300 in anon-deployed configuration and relative positioning of the three markerbands 326, 328, 330. During use of the device 300, the in vivo relativepositions of the marker bands 326, 328, 330, viewed fluroscopically,indicates the displacement of the distal ends 306, 312 of the inner andouter catheters and the consequent configuration of the filter valve, asdiscussed in more detail below.

A handle 332 is optionally provided at or adjacent the proximal ends ofthe inner and outer catheters 302, 308 (including tubular couplingmember 318) to controllably longitudially displace the inner and outercatheters relative to each other. By way of example only, the handle 322may include a standard slider assembly, e.g., in the form of a spool andshaft, that converts manual longitudinal movement of the user into adesired and controlled longitudinal displacement between the inner andouter catheters. As yet another alternative, the handle may include arotation knob 334 connected to a lead screw that converts manual userrotational movement into a desired and controlled longitudinaldisplacement between the distal ends of the inner and outer catheters,such as shown by arrow 336 (FIG. 3B).

The inner catheter 308 is between two and eight feet long, and has anouter diameter of between 0.67 mm and 3 mm (corresponding to cathetersizes 2 French to 9 French), and is made from a liner made offluorinated polymer such as polytetrafluoroethylene (PTFE) orfluorinated ethylene propylene (FEP), a braid made of metal such asstainless steel or titanium, or a polymer such as polyethyleneterephthalate (PET) or liquid crystal polymer, and an outer coating madeof a polyether block amide thermoplastic elastomeric resin such asPEBAX®, polyurethane, polyamide, copolymers of polyamide, polyester,copolymers of polyester, fluorinated polymers, such as PTFE, FEP,polyimides, polycarbonate or any other suitable material, or any otherstandard or specialty material used in making catheters used in thebloodstream.

The outer catheter 302 is comprised of polyurethane, polyamide,copolymers of polyamide, polyester, copolymers of polyester, fluorinatedpolymers, such as PTFE, FEP, polyimides, polycarbonate or any othersuitable material. The outer catheter 302 may also contain a braidcomposed of metal such as stainless steel or titanium, or a polymer suchas PET or liquid crystal polymer, or any other suitable material. Thewall thickness of the outer catheter 302 is preferably in the range of0.05 mm to 0.25 mm with a more preferred thickness of 0.1 mm-0.15 mm.

The distal end 340 of the filter valve 314 is fused or otherwise fixedlycoupled (both longitudinally and rotationally fixed) adjacent, butpreferably slightly proximally displaced from, the distal end 312 of theinner catheter 308, and the proximal end 342 of the filter valve isfused or otherwise coupled at or adjacent the distal end 306 of theouter catheter 302.

The filter valve 314 is composed of one, two, or more metal (e.g.,stainless steel or Nitinol) or polymer filaments 350, which form asubstantially closed shape when deployed and not subject to outsideforces. Where polymeric filaments are utilized, the filaments 350 may becomposed of PET, polyethylene-napthalate (PEN), liquid crystal polymer,fluorinated polymers, nylon, polyamide or any other suitable polymer. Ifdesired, when polymeric filaments are utilized, one or more metalfilaments may be utilized in conjunction with the polymeric filaments.According to one aspect of the invention, where a metal filament isutilized, it may be of radio-opaque material to facilitate tracking thefilter valve 314 and its configuration within the body. In a deployed,expanded diameter configuration, the filter valve 314 is capable ofbeing modified in shape by fluid forces. It is preferred that thefilaments 350 not be bonded to each between their ends so to enable thevalve to rapidly automatically open and close in response to dynamicflow conditions. The multiple filaments 350 of the filter valve arepreferably braided and can move relative to each other between theirends. As discussed hereinafter, the filaments are spring biased (i.e.,they have “shape memory”) to assume a desired crossing angle relative toeach other so that the valve can self-assume a desired shape.

In the device shown in FIG. 3A, the assumed shape in substantiallyspherical, though as described hereinafter the shape can besubstantially frustoconical. (For purposes herein the term“substantially spherical” should be understood to include not only asphere, but a generally rounded shape including a spherical portion or arounded oblong shape 314 a, such as shown in FIG. 4, or a portionthereof. For purposes herein the term “substantially frustoconical”should be understood to include not only a generally truncated cone, buta truncated hyperboloid, a truncated paraboloid, and any other shape 314b which starts from a circular proximal end 342 b at the distal end 306of the outer catheter 302 and diverges therefrom and returns to closeback down at the distal end 340 b of the filter valve adjacent thedistal end 312 of the inner catheter 308, as shown in FIG. 5). In allembodiments, the shape of the filter valve 314 is closed down at oradjacent the respective ends 306, 312 of the outer and inner catheters302, 308, and can be defined by a proximal hemispherical portion 346 anda distal hemispherical portion 348, or two conical portions, or aproximal spherical portion and a distal conical portion, or a proximalconical portion and a distal spherical portion, or any of the precedingwith an intervening shaped portion therebetween, which are joinedtogether at preferably the largest diameter ends of the respectiveportions. As such, it is appreciated that the proximal and distalportions 346, 348 of the filter valve 314 are not required to belongitudinally symmetrical, and may be asymmetrical, in construction,which is apparent in the non-deployed configuration of the filter valve314 shown in FIG. 3B. The joined proximal and distal portions each mayhave filaments oriented at a different braid angle, discussed below. Inaddition, the proximal and distal portions may be joined mechanicallyvia the ends of the filaments, or by the filter material, which isdiscussed in more detail below.

The filter valve 314 is designed to be manually reconfigured betweennon-deployed and deployed configurations by movement of the inner andouter catheters relative to each other, wherein in each of thenon-deployed and deployed configurations the distal end of the filtervalve extends outside and distally of the distal end of the outercatheter. As shown in FIGS. 3B and 6A, in the non-deployedconfiguration, the filter valve 314 is provided with a smaller maximumdiameter suitable for tracking the device over a guidewire 360 (FIG. 6A)through the vessels 362 to a treatment site. The inner catheter 308 isdisplaced distally relatively to the outer catheter 302 (in thedirection of arrow 380) to stretch or otherwise present the filter valvein an elongate configuration having a tapered tip which facilitatestrackability over the guidewire 360. In this collapsed, non-deployedconfiguration, the inner catheter 308 is preferably pushed as distal aspossible relative to the outer catheter 302. In a preferred embodiment,the non-deployed elongated configuration of the filter valve tapersdistally over at least 50%, and preferably at least 75%, of its length.

Then, referring to FIG. 6B, once the filter valve is positioned at thetreatment site in the vessel 362, the inner catheter 308 can beretracted relative to the outer catheter 302 (in the direction of arrow382) to expand the filter valve 314 and cause the filter valve to assume(initially) a partially deployed configuration within the vessel inwhich the filter valve does not seal against the vessel wall 362.Alternatively or thereafter, as shown in FIG. 6C, the inner catheter 308can be further retracted relative to the outer catheter 302 (asindicated by arrow 384) to more fully expand the filter valve 314 toseal against the vessel wall 362. This configuration of the filter valve314 is also shown in FIG. 7. When retracted into the configuration shownin FIG. 6B, the distal end of the filter valve 314 forms a distal facingplane or concave surface 368 (with it being understood that in thenon-deployed configuration of the filter valve presents a distal facingconvex or convexly conical surface), while the proximal facing surfaceremains unmodified in shape and is generally a smooth convex surface.Then, with the filter valve deployed, embolization agents 388 aredelivered under pressure distally through and out of the inner catheter,distal of the filter valve, and into the vessel. Delivery of theembolization agents in this manner will result in a downstream pressurechange that initially causes higher pressure distal of the filter valvethan upstream of the filter valve rapidly sealing to the vessel wall anddirecting all infusion pressure downstream. In its open position, thefilter valve stops embolization agents from traveling upstream past thefilter valve in a proximal ‘reflux’ direction. In addition, because thefilter valve is a closed shape and delivers the embolic distal of thefilter valve, 100% of the dose delivered is provided to the patient;i.e., without the potential for any of the dose to remain within thefilter valve. Further, the shape of the proximal surface of the deployedfilter valve presents reduced resistance to blood passing the filtervalve in the downstream direction, but presents a distal facing surfaceat a different orientation and one that is substantially perpendicularto the vessel wall and has significant resistance to flow in theupstream direction so as to prevent reflux.

Turning now to FIGS. 8A-8C, the above described radio-opaque first,second and third marker bands 326, 328, 330 facilitate determining thein vivo configuration of the filter valve. Referring to FIG. 8A, by wayof example only, when the three marker bands 326, 328, 330 are shownspaced apart, the filter valve 314 can be indicated to be in thenon-deployed configuration. In FIG. 8B, with the third marker band 330offset substantially closer to the second marker band 328, the filtervalve 314 can be indicated to be in a partially deployed configuration,with the inner catheter 308 somewhat retracted relative to the outercatheter 302. FIG. 8C, under fluoroscopy, would show two bands 326, 328,with the second marker band hiding the third marker band 330 (FIG. 8B),indicating the fully deployed configuration. Other relativerelationships of the marker bands are possible to provided fluoroscopicindicia with respect to the state of the filter valve.

Referring now to FIG. 9, when the filter valve is advanced to atreatment site within a vessel in the non-deployed configuration, a verysmall pressure differential (e.g., 2.5 mmHg) is generated between theproximal and distal sides of the filter valve. When the filter valve ispartially opened, i.e., deployed but not extending to the vessel wall(indicated in FIG. 9 as deployed ‘25%’), a small but relatively largerpressure differential (e.g., 5 mmHg) is generated between the proximaland distal sides of the filter valve. When the filter valve is fullyopened so that the filter valve contacts the vessel wall (indicateddeployed ‘50%’), a larger pressure differential (e.g., 10 mmHg) isgenerated between the proximal and distal sides of the filter valve.When the filter valve is fully opened and an infusate is infused throughthe orifice of the inner catheter to a location distal of the filtervalve, a significantly larger pressure differential (e.g., 10-20 mmHg)is generated between the proximal and distal sides of the filter valve.Referring to FIGS. 10A-10C, the range of generated pressuredifferentials can be used to selectively treat vessels of differentdiameter downstream of the filter valve. Referring to FIG. 10A, withsignificant generated flow and a pressure drop between the proximal anddistal sides of the filter valve, the infusate is directed downstream toat least the largest target vessel 370. Then, referring to FIG. 10B, bygenerating an increase in pressure differential by raising the fluidpressure of the infusate, additional smaller target branch vessels 372resistant to the perfusion at the initial infusate pressure areperfused. Finally, referring to FIG. 10C, by increasing the pressuredifferential again, even smaller target branch vessels 374 can beperfused. Similarly, to the extent that treatment is intended to belimited to only certain vessels, the distal pressure can be limit tobelow that required to perfuse the smaller vessels.

According to one aspect of the invention, the valve is preferablycapable of being configured into its closed position after theembolization treatment procedure is completed for removal from thepatient. In one configuration for post-treatment removal from thepatient, the valve is simply withdrawn in the deployed configuration. Inanother configuration, the inner catheter 308 is further retractedrelative to the outer catheter 302 to invert a portion or all of thedistal filter valve 348 into the proximal valve 346 to contain embolicagent that may potentially remain on the filter valve after thetreatment. In yet another configuration, as shown in FIG. 6D, the innercatheter is even further retracted relative to the outer catheter (inthe direction of arrow 386) to invert the entire filter valve 314 intothe outer catheter 302 to fully contain any embolic agent that maypotentially remain on the filter valve after the treatment.

Now, as discussed in previously incorporated U.S. Pat. No. 8,696,698,three parameters help define the performance and nature of the deployedfilter valve: the radial (outward) force of the valve, the time constantover which the valve changes condition from closed to open, and the poresize of the filter valve.

In a preferred embodiment, the filter valve expands into the deployedconfiguration when, first, the inner and outer catheter are displaced tomove the distal end of the filter valve relative to the proximal end ofthe filter valve and thereby shorten and expand the valve into thedeployed configuration. However, once deployed, the filter valve fullyexpands to the vessel wall (i.e., reaches an open condition) when thepressure at the distal orifice of the inner catheter is greater than theblood pressure. The filter valve is also in a deployed but closedcondition (with filter valve retracted from the vessel wall) when bloodis flowing upstream, or in a proximal to distal direction, with pressuregreater than the pressure at the inner catheter orifice. In addition,when the radial force of expansion on the filter valve (i.e., theexpansion force of the filter valve itself in addition to the force ofpressure in the distal vessel over the distal surface area of the valve)is greater than the radial force of compression on the filter valve(i.e., force of pressure in the proximal vessel over the proximalsurface area of the filter valve), the filter valve fully expands sothat the valve assumes the open configuration. Thus, the radial force ofexpansion of the filter valve is chosen to be low (as described in moredetail below) so that normal blood flow in the downstream distaldirection will prevent the deployed filter valve from reaching the opencondition. This low expansion force is different than the expansionforces of prior art stents, stent grafts, distal protection filters andother vascular devices, which have significantly higher radial forces ofexpansion. It is appreciated that expansion force is sufficiently lowthat it will not cause the inner catheter to move relative to the outercatheter; such relative movement is preferably effected only by the userof the device. Thus, once the filter valve is in the deployedconfiguration in the vessel, the filter valve is dynamically movable(opens and closes) depending on the local fluid pressure about thefilter valve: when the fluid pressure is higher on the proximal side ofthe filter valve, the filter valve assumes a relatively contractedconfiguration with a first diameter smaller than the diameter of thevessel such that fluid flow about the filter valve is permitted, andwhen the fluid pressure is higher on the distal side of the filtervalve, the filter valve assumes an expanded configuration with a seconddiameter relatively larger than the first diameter in which the filtervalve is adapted to contact the vessel wall.

The radial force of expansion of a braid is described by Jedwab andClerc (Journal of Applied Biomaterials, Vol. 4, 77-85, 1993) and laterupdated by DeBeule (DeBeule et al., Computer Methods in Biomechanics andBiomedical Engineering, 2005) as:

$F = {2{n\left\lbrack {{\frac{{GI}_{p}}{K_{3\;}}\left( {\frac{2\sin\;\beta}{K_{3}} - K_{1}} \right)} - {\frac{{EI}\;\tan\;\beta}{K_{3}}\left( {\frac{2\cos\;\beta}{K_{3}} - K_{2}} \right)}} \right\rbrack}}$

where K₁, K₂, K₃ are constants given by:

$K_{1} = \frac{\sin\; 2\beta_{0}}{D_{0}}$$K_{2} = \frac{2\cos^{2}\beta_{0}}{D_{0}}$$K_{3} = \frac{D_{0}}{\cos\;\beta_{0}}$

and I and I_(p) are the surface and polar moments of inertia of thebraid filaments, E is the Young's modulus of elasticity of the filament,and G is the shear modulus of the filament. These material propertiesalong with the initial braid angle (β₀), final braid angle (β), stentdiameter (D₀), and number of filaments (n) impact the radial force ofthe braided valve.

In one examplar embodiment, the filter valve 314 is composed oftwenty-four polyethylene terephthalate (PET) filaments 350, each havinga diameter of 0.1 mm and pre-formed to an 8 mm diameter mandrel and abraid angle of 130° (i.e., the filaments are spring-biased or have ashape memory to assume an angle of 130° relative to each other when thevalve assumes a fully deployed state and opens in a frustoconicalconfiguration). The filaments 350 preferably have a Young's modulusgreater than 200 MPa, and the filter valve 314 preferably has a radialforce of less than 40 mN in the fully deployed position (i.e., where thefilaments assume their shape memory). More preferably, the filter valve314 has a radial force in the fully deployed position of less than 20mN, and even more preferably the filter valve has a radial force ofapproximately 10 mN (where the term “approximately” as used herein isdefined to mean±20%) in the deployed position.

In one embodiment, when subject to an infusion pressure at the distalorifice 358 of the inner catheter, the filter valve 314 moves betweendeployed positions allowing downstream fluid passage (closed) andpreventing fluid passage (open) in a static fluid (e.g., glycerin)having a viscosity approximately equal to the viscosity of blood (i.e.,approximately 3.2 cP) in 0.067 second. For purposes herein, the time ittakes to move from the closed position to the open position in a staticfluid is called the “time constant”. According to another aspect of theinvention, the filter valve 314 is arranged such that the time constantof the filter valve 314 in a fluid having the viscosity of blood isbetween 0.01 seconds and 1.00 seconds. More preferably, the filter valve314 is arranged such that the time constant of the filter valve in afluid having the viscosity of blood is between 0.05 and 0.50 seconds.The time constant of the filter valve 314 may be adjusted by changingone or more of the parameters described above (e.g., the number offilaments, the modulus of elasticity of the filaments, the diameter ofthe filaments, etc.).

According to one aspect of the invention, the deployed filter valveopens and closes sufficiently quickly to achieve high capture efficiencyof embolic agents in the presence of rapidly changing pressureconditions. More particularly, as shown in FIG. 6C, with the inner andouter catheter displaced to open the filter valve to the vessel wall362, when pressure at the distal orifice 358 of the inner catheter 308(distal of the deployed filter valve 314) increases higher than thepressure in the blood vessel 362, the seal between the periphery of thefilter valve and the vessel wall is increased, thus blocking refluxingembolics. It is important to note that pressure is communicatedthroughout the vasculature at the speed of sound in blood (1540 m/s) andthat the valve opens and closes in in response to pressure changeswithin the blood vessel. Since the expandable filter valve responds topressure changes, it reacts far faster than the flow rates of embolicsin the blood (0.1 m/s) thereby preventing reflux of any embolics.

As will be appreciated by those skilled in the art, the braid geometryand material properties of the filaments 350 are intimately related tothe radial force and time constant of the filter valve. Since, accordingto one aspect of the invention, the filter valve is useful in a varietyof vessels of different diameters and flow conditions, eachimplementation can have a unique optimization. By way of example only,in one embodiment, the filter valve 314 has ten filaments 350, whereasin another embodiment, the filter valve has forty filaments 350. Anysuitable number of filaments can be used. Preferably, the diameter ofthe filaments are chosen in the range of 0.025 mm to 0.127 mm, althoughother diameters may be utilized. Preferably, the pitch angle (i.e., thecrossing angle assumed by the braided filaments in the fully opendeployed position) is chosen in the range of 100° to 150°, althoughother pitch angles may be used. Preferably, the Young's modulus of thefilament is at least 100 MPa, and more preferably at least 200 MPa.

The filter valve 314 is chosen to have a pore size which is small enoughto capture (filter) embolic agents in the blood stream as the bloodpasses through the filter valve. Where large embolic agents (e.g., 500μm) are utilized, it may be possible for the filaments alone to actdirectly as a filter to prevent embolic agents from passing through thevalve (provided the filaments present pores of less than, e.g., 500 μm).Alternatively, a coating 364 is preferably added to the filaments 350,and more preferably to the formed braid structure, to provide the filterfunction. Such a separate polymeric filter is particularly useful wheresmaller embolic agents are utilized. The polymeric filter can be placedonto the braid structure by spraying, spinning, electrospinning, bondingwith an adhesive, thermally fusing, mechanically capturing the braid,melt bonding, dip coating, or any other desired method. The polymericcoating 364 can either be a material with pores such as ePTFE, a solidmaterial that has pores added such as polyurethane with laser drilledholes, or the filter coating can be a web of very thin filaments thatare laid onto the braid. Where the coating 364 is a web of thinfilaments, the characteristic pore size of the filter can be determinedby attempting to pass beads of different diameters through the filterand finding which diameter beads are capable of passing through thefilter in large quantities. The very thin filaments can be spun onto arotating mandrel according to U.S. Pat. No. 4,738,740 with the aid of anelectrostatic field or in the absence of an electrostatic field or both.The filter thus formed can be adhered to the braid structure with anadhesive or the braid can be placed on the mandrel and the filter spunover it, or under it, or both over and under the braid to essentiallycapture it. The filter 364 can have some pores formed from spraying orelectrospinning and then a secondary step where pores are laser drilledor formed by a secondary operation. In the preferred embodiment amaterial capable of being electrostatically deposited or spun is used toform a filter on the braid, with the preferred material being capable ofbonding to itself. The filter may be made of polyurethane, pellethane,polyolefin, polyester, fluoropolymers, acrylic polymers, acrylates,polycarbonates, or other suitable material. The polymer is spun onto thebraid in a wet state, and therefore it is desirable that the polymer besoluble in a solvent. In the preferred embodiment, the filter is formedfrom polyurethane which is soluble in dimethylacetamide. The polymermaterial is spun onto the braid in a liquid state, with a preferredconcentration of 5-10% solids for an electrostatic spin process and15-25% solids for a wet spin process.

According to one aspect of the invention, the filter coating 364 has acharacteristic pore size between 10 μm and 500 μm. More preferably, thefilter has a characteristic pore size between 15 μm and 100 μm. Evenmore preferably, the filter has a characteristic pore size of less than40 μm and more preferably between 20 μm and 40 μm. Most desirably, thefilter is provided with a characteristic pore size that will permitpressurized blood and contrast agent to pass therethrough while blockingpassage of embolizing agent therethrough. By allowing regurgitatingblood and contrast agent to pass through the filter in a direction fromdistal the valve toward the proximal end of the valve, the contrastagent may be used to indicate when the target site is fully embolizedand can serve to identify a clinical endpoint of the embolizationprocedure. Therefore, according to one aspect of the invention, thevalve allows the reflux of the contrast agent as an indicator of theclinical endpoint while preventing the reflux of the embolization agentsat the same time. In addition, by allowing blood to flow back throughthe filter material, even at a relatively slow rate, backpressure on thedistal side of the valve can be alleviated.

The filter valve is also preferably provided with a hydrophilic coating,hydrophobic coating, or other coating that affects how proteins withinblood adhere to the filter and specifically within the pores of thefilter. More specifically, the coating is resistant to adhesion of bloodproteins. One coating that has been used successfully is ANTI-FOGCOATING 7-TS-13 available from Hydromer, Inc. of Branchburg, N.J., whichcan be applied to the filter by, e.g., dipping, spraying, roll or flowcoating.

By appropriate design of the pore size and use of an appropriatecoating, proteins in the blood will almost immediately fill the poresduring use. The proteins on the coated porous filter operate as apressure safety valve, such that the pores are filled with the proteinswhen subject to an initial fluid pressure greater than the blood vesselpressure, but the proteins are displaced from the pores and the poresare opened to blood flow at higher pressures such as a designatedthreshold pressure. The designated threshold pressure is determined toprevent damage to the tissue and organs, and injury to the patient.Thus, this system allows a pressure greater than the vessel pressurewhile limiting very high pressures which may be unsafe to the patient.As such, the system provides pressure regulation which is not possiblewith other occlusive devices, including balloons. Notwithstanding theadvantage of the above, it is not a requirement of the invention thatthe filter be constructed to allow either blood or contrast agent topass through in the upstream ‘reflux’ direction under any determinedpressure.

It is recognized that in the open state, proteins in the blood mayrapidly fill the pores of the filter valve. However, as discussed above,should a threshold pressure be reached, the filter valve is designed topermit the blood to reflux through the pores of the filter valve whilestill blocking the passage of the embolic agent. An exemplar thresholdpressure is 180 mmHg on the distal surface of the filter valve, althoughthe device can be designed to accommodate other threshold pressures.Such can be effected, at least in part, by the use of an appropriatecoating on the filter that facilitates removal of the blood proteinsfrom within the filter pores when subject to threshold pressure. Thisprevents the vessel in which the device is inserted from being subjectto a pressure that could otherwise result in damage. Nevertheless, it isnot necessary that blood and contrast agent be permitted to refluxthrough the valve.

In an embodiment, the filter coating 350 is preferably provided as ahomogenous coating of filaments, with the proximal and distal portions346, 348 of the filter valve 314 having a uniform coating construct. Asthe filter valve 314 is provided in the form of a closed shape, with itsproximal end 346 fused to the outer catheter 302, and its distal end 348fused to the inner catheter 308, it is appreciated that any fluid oragent passing from the vessel and through the filter must through twosimilar layers of the filter; i.e., a layer at the proximal side of thefilter valve and a layer at the distal side of the filter valve.

In accord with one aspect of the invention, the filter valve has adifferent radial force at its proximal portion relative to its distalportion. This difference in radial force enables behavior that isdependent on the direction of the flow (i.e. the valve behavior). It ispreferred that the distal portion have lower radial force than theproximal portion, as described in FIGS. 11-16, as follows.

Turning now to FIG. 11, another filter valve 414 at the distal end of amicrovalve device 400 is shown. The filter valve 414 includes aheterogeneous filter coating in which the entire filter valve is coated.The coating 450 includes smaller pores at the proximal portion 426 ofthe filter valve, and larger pores at the distal portion 428. By way ofexample only, the smaller pores can be on the order to one micron,whereas the larger pores can be on the order to 30 microns. Thedifference in pore size may be provided by placing more of the samefilamentary coating at the proximal portion and relatively less at thedistal portion to provide a greater radial force in the proximal portioncompared to the distal portion. The difference in radial force allowsthe filter valve to have different performance in forward flow comparedto backflow. In forward flow, the device remains in a conical shapeallowing fluid around it. In backflow, the very weak structure collapsesinward, allowing fluid pressure to seal the device against the vesselwall and reducing backflow.

Referring now to FIG. 12, yet another embodiment of a filter valve 514at the distal end of a microvalve device 500 is shown. The filter valve514 includes a heterogenous filter coating in which the entire filtervalve is coated. The coating 550 includes a non-porous membrane providedat the proximal portion 526 of the filter valve, and a porousfilamentary coating at the distal portion 528. The non-porous membranedoes not allow flow through the membrane, thus increasing the antegradeflow around the device in forward flow. The porous membrane on thedistal portion allows flow through the device, which expands the filtervalve to the wall in backflow to more effectively block embolic agentsfrom flowing backward.

Turning now to FIG. 13, another embodiment of a filter valve 614 isshown. The filter valve has a non-porous membrane coating 690 at itsinner surface 692 of the proximal portion, and a filter coating 650 onthe outer surface of at least the distal portion of the filter valve,and preferably the entire filter valve. The combination of a non-porousmembrane and porous membrane on the proximal portion both increasesantegrade flow and radial strength in forward flow while the porousmembrane on the distal portion reduces radial strength and allows flowinto the filter valve in back flow to seal the vessel and block thereflux of embolic agents.

Referring now to FIG. 14, another embodiment of the filter valve 714 isshown. The filter valve has a construction with a variable braid angle;i.e., with different braid angles at different portions of the filtervalve. In the illustrated embodiment, the braid angle is lower at theproximal end and higher at the distal end. The lower braid angle, e.g.,at 792, is preferably in the range of 60-90°, and the higher braidangle, e.g., at 794, is preferably greater than 110°. Lower braid anglehas a greater stiffness than lower braid angle, again providing adifferent operating behavior in forward flow compared to backward flow.The variable braid angle aspect of the device can be used in conjunctionwith any other embodiment described herein.

Turning now to FIG. 15, another embodiment of a filter valve 814substantially as described with respect to a device 300 above, is shown.Filter valve 814 is distinguished in having a thicker braid 827 at itsproximal portion 826, and a relatively thinner braid 829 at its distalportion 828. The so-called thinner braid 829 may be the result of aconstruction of individually thinner braid filaments 831 in a similarbraid form as in the proximal portion 826, or a like size braid filamentas in the proximal portion but presented in a denser latticeconstruction in the proximal construction and a wider, less denselattice construction across the distal portion of the filter valve, or acombination of these two structural design elements. In addition, thefilaments of the proximal and distal portions may be otherwise designedto exert differentiated radial force (with greater force at the proximalportion). By way of the example, the filaments of the braid in theproximal portion may be selected to have increased resiliency or springforce, regardless of size or spacing, so as to operate as desired. Theproximal and distal portions 826, 828 are preferably demarcated by thecircumference about the maximum diameter 833 of the filter valve. Theproximal and distal portions 826, 828 may have either homogeneous filtercoatings (discussed above with respect to FIGS. 4 and 5) orheterogeneous filter coatings (discussed above with respect to FIGS.11-13), and common (discussed above with respect to FIGS. 4 and 5) ordifferent braid angles (discussed above with respect to FIG. 14).

Referring to FIG. 16, another embodiment of a filter valve 914 for adevice as substantially as described with respect to 300 above, isshown. The filter valve 914 includes a proximal filamentary braidedportion 926, preferably coated with a polymeric filter material 927, anda distal portion comprising a polymeric filter material 928. Theproximal and distal portions 926, 928 are preferably demarcated by thecircumference about the maximum diameter 933 of the filter valve. Inaccord with this embodiment, the distal portion 928 is braidless; i.e.,does not include any of the self-expanding filamentary structure. Thefilter valve 914 may be formed by positioning the filamentary braid forthe proximal portion 926 on a mandrel (not shown), and spray coating aporous polymeric membranous material over the proximal braid and alsofurther distally onto the mandrel—where no braid is provided—forconstruction of the braidless distal portion 928. After curing, theconstruct is removed from the mandrel. Once the proximal portion 926 ofthe filter valve 914 is coupled to the outer catheter 904, and thedistal portion 928 of the filter valve 914 is coupled to the innercatheter 908, the filter valve has preferred properties. At the distalportion 928, the filter valve 914 is structured substantially similarlyto a fabric. That is, when the inner catheter 908 is advanced relativeto the outer catheter 904 and the distal portion 928 is placed undertension, the distal portion 928 of the filter valve 914 is strong undertensile force; however, when the inner catheter 908 is retractedrelative to the outer catheter 904 and the distal portion 928 is placedunder compression, the distal portion of the filter valve is floppyunder compression force.

Turning now to FIGS. 17A-18, another embodiment of a filter valve 1014substantially as described with respect to a device 300 above, is shown.Filter valve 1014 is distinguished in having a braided structure 1027 offilaments 1027 a at its proximal portion 1026, and a spiral arrangement1029 of filaments 1029 a at its distal portion 1028, seen best in FIG.18. The braided structure 1027 includes filaments 1027 a crossing overand under one another, e.g., in a woven configuration, to define acrossing angle at the junctions of the filaments. The spiral arrangement1029 includes fewer filaments 1029 a than the braided structure 1027, inwhich such fewer filaments 1029 a extend preferably without crossingover and under the other filaments in the distal portion 1028, such thatthe distal portion is preferably non-braided for desired forceapplication, as discussed below. The proximal and distal portions 1026,1028 are preferably demarcated by the circumference about the maximumdiameter 1033 of the filter valve 1014. Each of the braided structure1027 and spiral arrangement 1029 are provided with a filter coating1050, preferably as described above with respect to coating 350 ondevice 300. The braided and spirally arranged filaments 1027 a, 1029 a,including the strand counts in each of the proximal and distal portions,the lengths of the respective filaments, and the diameters of therespective filaments, and the materials of the respective filaments, canbe individually or collectively optimized for an intended resultantapplied radial force within the vessel. By way of example only, thedistal spiral arrangement may include three, six, twelve, or twentyspiral wound filaments. In addition, the spirally arranged filaments1029 a in the distal portion 1028 can be evenly circumferentially spacedabout the distal portion; i.e., each filament 1029 a is equidistantlydisplaced between its two surrounding filaments (FIG. 18), or can havespirally configured filaments 1129 a arranged in groups 1131 such thatthe filaments have a variable relative displacement between each otheror between groups of filaments (FIG. 19). By way of example, FIG. 19shows groups 1131 of two filaments, but groups of three, four and six,or a combination of groups of different numbers of filaments are alsocontemplated within the scope of the present disclosure. Also, while aclockwise (CW) direction of the spiral arrangement is shown in FIGS.17A-18, it is appreciated that the filaments may be configured in acounterclockwise (CCW) configuration, or for some of the filaments 1129a to extend in the CW direction and the remainder of the filaments 1129b to extends in the CCW direction, as shown in FIG. 19. However, wheresome filaments extend in each of the CW and CCW direction, suchfilaments preferably extend between the counter-rotational groups orsets (as shown) so as to prevent interference, or in separate ‘planes’or layers of the distal portion such that the filaments do not crossover and under the counter-directional filaments.

The filter valve 1014 may be formed by providing a braided filamentarytubular construct, and selective selective removal certain filaments andspiral wound manipulation of remaining filaments at a distal portion ofa braided filamentary tubular construct, while keeping the filamentsstructure of the proximal braided portion intact. Then, the resultantfilamentary construct is filter coated. In such construct, it isappreciated that filaments defining the braided structure of theproximal portion and filaments defining the spiral wound structure ofthe distal portion may be continuous. As such, in this construct, theproximal filaments referred to herein are to be considered the proximalportion of such filaments, whereas the distal filaments referred toherein are to be considere the distal portion of such same filaments.Alternatively, the filamentary constructs of the proximal and distalportions 1026, 1028 may be separately formed and subsequently joined,and then coated with the filter coating 1050. Other manufacturingprocesses may also be used.

In use, with the filter valve 1014 provided on the distal ends of outerand inner catheters 1004, 1008, as described above, the inner catheter1008 is distally displaced relative to the outer catheter 1004 to reducethe diameter of the filter valve 104, as shown in FIG. 17A for insertioninto a patient. This configuration facilitates tracking over a guidewireto a location of therapeutic treatment. The spiral filamentconfiguration of the distal portion 1028 of the filter valve offers alower profile at the distal end of the device. Once at the therapy site,the guidewire can be removed. Then, the user begins to proximallydisplace the inner catheter 1008 relative to the outer catheter 1004 toretract the distal end portion 1028 relative to the proximal braidedportion 1026 in preparation for treatment (FIG. 17B). Upon fullretraction of the distal portion 1028, the spiral filament “struts” 1029a push radially outward, driving the braided section 1028 diametricallyradially outward until the circumference reaches its largest potentialdiameter 1033 (FIG. 17C); i.e., in contact with the vessel wall. At thispoint the spiral filament “struts” start to reverse in rotationaldirection, and essentially pull within the braided proximal portion ofthe filter valve. As such, in this embodiment, a hinge-point is createdat the transition from spiral to braid. Further, the filter valve 1014has a higher potential force at the braided proximal portion 1026 thanat spiral filament distal portion 1028.

In each of the embodiments of FIGS. 11-19, the distal portion of thefilter valve exerts a significantly reduced radial force relative to theproximal portion of the filter valve, which results in optimizing thefunction of the filter valve as a valve. In forward (downstream) flow ofthe fluid within the vessel, as the fluid contacts the proximal side ofthe expanded proximal portion, the fluid flows around filter valve. Indistinction, in backward or reflux (upstream) flow of fluid within thevessel as the fluid contact the distal side of the expanded distalportion, the fluid flows into—and not around—the filter valve. In suchupstream flow, certain fluids, namely blood, are able to flow throughthe double layer filter material of the filter valve, while the pores ofthe filter material are of a sufficiently small size to capture embolicagents and other therapeutic agents of interest.

In any of the embodiments, the physician will track and advance theinner catheter of the microvalve device over a guidewire out to a targetlocation, and then remove the guidewire. An embolic agent is theninfused through the inner catheter to deliver the agent distal of themicrovalve, and the device is utilized as intended and in accord withits specific structural design. Then, after infusion, when it isnecessary to remove the device from the patient, the physician has twooptions to prepare or configure the microvalve device for removal. Theinner catheter can be pushed or otherwise displaced forward relative tothe distal end of the outer catheter to result in collapse of themicrovalve to reduce its diameter to facilitate its removal from thevessels of the body. Alternatively, after infusion of the agent, theinner catheter can be proximally withdrawn and inverted into the distalend of the outer catheter to retain at least a portion, and preferablyall, of the microvalve device within the outer catheter and capture anyembolic agent on such portion of the microvalve within the outercatheter during subsequent withdrawal of the device from the patient.The second option is preferred for radioactive embolic agents where thepotential for spreading radioactive embolics during removal canotherwise exist.

In any of the embodiments described herein, the components of the valvemay be coated to reduce friction in deployment and retraction. Thecomponents may also be coated to reduce thrombus formation along thevalve or to be compatible with therapeutics, biologics, or embolics. Thecomponents may be coated to increase binding of embolization agents sothat they are removed from the vessel during retraction.

According to one aspect of the invention, the catheter body and mesh maybe separately labeled for easy visualization under fluoroscopy. Thecatheter body can be labeled by use of any means known in the art; forexample, compounding a radio-opaque material into the catheter tubing.The radio-opaque material can be barium sulfate, bismuth subcarbonate orother material. Alternatively or additionally, radio-opaque medium canbe compounded into the materials of the braid and the filter. Or, aspreviously described, one or more of the filaments may be chosen to bemade of a radio-opaque material such as platinum iridium.

In each of the embodiments, the inner catheter may be a single lumen ora multi-lumen catheter. Preferably, the catheter has at least one lumenused to deliver the embolization agents, and one or more additionallumen may be provided, if desired, for passage of a guidewire or otherdevices or to administer fluids, e.g., for flushing the artery after theadministration of embolization agents.

The above apparatus and methods have been primarily directed to a systemwhich permits proximal and distal flow of biological fluid (e.g., blood)within a body vessel, and which prevents reflux of an infusate past thevalve in a proximal direction. It is appreciated that the valve may alsobe optimized to reduce blood flow in the distal direction. In any of theembodiments, the radial force of the filter valve can be tuned byadjusting the braid angle. Tuning the radial force allows the blood flowto be reduced by up to more than 50 percent. By way of example,providing a braid angle greater than 130° will significantly reduceblood flow past the valve in the distal direction, with a braid angle ofapproximately 150° slowing the blood flow by 50 to 60 percent. Otherbraid angles can provide different reductions in distal blood flow. Thereduced distal blood flow can be used in place of a ‘wedge’ technique,in which distal blood flow is reduced for treatment of brain and spinalarteriovenous malformations. Once the blood flow is slowed by the valve,a glue such as a cyanoacrylic can be applied at the target site.

While the above description has been primarily directed to use of thedevice for infusing a therapeutic agent, it is appreciated that thedevice has significant functionality even when delivery of a therapeuticagent is not the primary function. By way of example, the device can beused to retrieve a thrombus and prevent dislodged embolic particles fromescaping into the patient's blood. Briefly, a thrombus retrieval devicecan be passed through the inner catheter 308 to release and retrieve athrombus. The filter valve 314 operates to prevent the thrombus andspray of embolic particles from passing beyond the filter valve and intothe vessel. Then when the thrombus is captured, the thrombus along withany embolic particles can be contained within the filter valve as thefilter valve is inverted into the outer catheter for removal from thepatient, in a similar method to that discussed above. For such use, theinner catheter may include a single lumen or multiple lumens; i.e., onefor the thrombus retrieval device and one or more for additional devicesor therapeutic agent infusion.

There have been described and illustrated herein multiple embodiments ofdevices and methods for reducing or preventing reflux of embolizationagents in a vessel. While particular embodiments of the invention havebeen described, it is not intended that the invention be limitedthereto, as it is intended that the invention be as broad in scope asthe art will allow and that the specification be read likewise. Thus,while various materials have been listed for the valve filaments, thevalve filter, and the inner and outer catheters, it will be appreciatedthat other materials can be utilized for each of them in each of thevarious embodiments in combination and without limitation. Also, whilethe invention has been described with respect to particular arteries ofhumans, it will be appreciated that the invention can have applicationto any blood vessel and other vessels, including ducts, of humans andanimals. In particular, the apparatus can also be used in treatments oftumors, such as liver, renal or pancreatic carcinomas. Further, theembodiments have been described with respect to their distal endsbecause their proximal ends can take any of various forms, includingforms well known in the art. By way of example only, the proximal endcan include two handles with one handle connected to the inner catheter,and another handle connected to the outer catheter. Movement of onehandle in a first direction relative to the other handle can be used toextend the filter valve in the non-deployed configuration foradvancement to the treatment site, and movement of that handle in anopposite second direction can be used to deploy the filter valve.Depending upon the handle arrangement, filter valve deployment can occurwhen the handles are moved away from each other or towards each other.As is well known, the handles can be arranged to provide for linearmovement relative to each other or rotational movement. If desired, theproximal end of the inner catheter can be provided with hash-marks orother indications at intervals along the catheter so that movement ofthe handles relative to each other can be visually calibrated and givean indication of the extent to which the valve is opened. It willtherefore be appreciated by those skilled in the art that yet othermodifications could be made to the provided invention without deviatingfrom its spirit and scope as claimed.

What is claimed is:
 1. A method of a using a microvalve device in ablood vessel, comprising: a) advancing a guidewire through the bloodvessel; b) providing the microvalve device including, i) a flexibleouter catheter having a proximal end and a distal end, ii) a flexibleinner catheter having a proximal end and a distal end with an orifice,the inner catheter extending through and longitudinally displaceablerelative to the outer catheter, and iii) a filter valve having aproximal end and a distal end, the proximal end of the filter valvecoupled to the distal end of the outer catheter, and the distal end ofthe filter valve coupled to the inner catheter at a location spacedproximal relative to the distal end of the inner catheter such that theinner catheter protrudes beyond the filter valve, wherein longitudinaldisplacement of the inner catheter relative to the outer catheter causesthe filter valve to reconfigure from a non-deployed configuration to adeployed configuration; c) with the distal end of the inner catheterlongitudinally advanced a first distance relative to the distal end ofthe outer catheter such that the filter valve assumes a first diameter,advancing the filter valve over the guidewire; d) once the filter valvereaches a target location, the distal end of the inner catheter isretracted relative to the distal end of the outer catheter such that thedistal end of the inner catheter is longitudinally advanced by a seconddistance smaller than the first distance relative to the distal end ofthe outer catheter such that the filter valve assumes a second diameterlarger than the first diameter; e) subsequent to d), further retractingthe distal end of the inner catheter relative to the distal end of theouter catheter such that the distal end of the inner catheter islongitudinally advanced by a third distance relative to the distal endof the outer catheter to cause at least a distal portion of the filtervalve to invert into the outer catheter and cause the filter valve tohave a planar or a concave distal face while the distal end of the innercatheter protrudes beyond both the filter valve and the outer catheter;and f) infusing a therapeutic agent through the microvalve device, outof the orifice of the inner catheter, and beyond the filter valve. 2.The method according to claim 1, further comprising: after step c),removing the guidewire from the inner catheter.
 3. The method accordingto claim 1, wherein: further retracting the distal end of the innercatheter relative to the distal end of the outer catheter causes thefilter valve to contact a wall of the blood vessel.
 4. The methodaccording to claim 3, wherein: the filter valve includes a plurality oflongitudinal filaments, and when advancing the filter valve over theguidewire, the filaments extend in a first rotational direction, andwhen the inner catheter is retracted relative to the outer catheter, thefilaments are extended in an opposite second rotational direction. 5.The method according to claim 1, wherein: the filter valve includes aplurality of filaments that are biased to expand a diameter of thefilter valve, the filaments adapted to automatically move the filtervalve from the non-deployed configuration to the deployed configurationif the inner and outer catheters are not otherwise subject tolongitudinal displacement.
 6. The method according to claim 5, wherein:once the filter valve is in the deployed state in the blood vessel, thefilter valve is dynamically movable depending on a local fluid pressureabout the filter valve, such that, when the fluid pressure is higher ona proximal side of the filter valve, the filter valve assumes aconfiguration with a first diameter smaller than the diameter of thevessel such that fluid flow about the filter valve is permitted, andwhen the fluid pressure is higher on a distal side of the filter valve,the filter valve assumes a configuration with a second diameterrelatively larger than the first diameter and in which the filter valveis adapted to contact the vessel wall.
 7. The method according to claim1, wherein: the filter valve has a proximal portion comprising a braidedfilamentary structure.
 8. The method according to claim 7, wherein: thefilter valve has a distal portion comprising a spiral filamentarystructure.
 9. The method according to claim 8, wherein: the spiralfilamentary structure is non-braided.
 10. The method according to claim1, wherein: the filter valve includes a polymeric filter on at least aproximal portion of the filter valve.
 11. The method according to claim10, wherein: the polymeric filter is also provided to a distal portionof the filter valve.
 12. The method according to claim 1, wherein: atleast a proximal portion of the filter valve comprises the closedfiltering portion.
 13. The method according to claim 1, wherein: aproximal portion and a distal portion of the filter valve comprise aclosed filtering portion.
 14. The method according to claim 1, furthercomprising: infusing a lubricating fluid into an annular space betweenthe inner and outer catheters.
 15. The method according to claim 1,wherein: the filter valve in the non-deployed configuration, has anelongated length between the proximal and distal ends of the filtervalve and, in the deployed configuration, the filter valve tapersdistally over at least 50% of the elongated length.